4975-73-9Relevant articles and documents
Polymemc conjugates of 9-[2-(phosphonomethoxy)ethyl]purine with potential antiviral and cytostatic activity
Pechar, Michal,Braunova, Alena,Subr, Vladimir,Ulbrich, Karel,Holy, Antonin
, p. 1211 - 1220 (2006)
Syntheses and characterization of polymer conjugates of 9-[2-(phosphonomethoxy)ethyl] (PME) derivatives of adenine (PMEA), 2,6-diaminopurine (PMEDAP) and guanine (PMEG) are described. The phosphonate group of these acyclic nucleotide analogues was activated by reaction with triphenylphosphine and di(2-pyridyl) disulfide (TPP-PDS). The activated phosphonate reacted with a random copolymer containing N-(2-hydroxypropyl) methacrylamide (HPMA) and N-(3-methacrylamidopropanoyl)ethane-1,2-diamine (Ma-AP-ED) units. The phosphonamide bond between the nucleotide and polymer carrier proved to be relatively stable at physiological pH 7.4 while at pH 5.0 (corresponding to endosomal or lysosomal compartments of cells) underwent slow hydrolysis. The rate of hydrolysis (drug release) was shown to depend on the detailed structure of the heterocyclic base. The polymer-drug conjugates described in the paper represent a new family of antiviral and cytostatic drugs with potentially improved pharmacokinetics, sustained drug release and diminished non-specific toxicity.
Catalytic C-N bond formation in guanylation reaction by N-heterocyclic carbene supported magnesium(II) and zinc(II) amide complexes
Baishya, Ashim,Barman, Milan Kr.,Peddarao, Thota,Nembenna, Sharanappa
, p. 112 - 118 (2014/09/17)
The catalytic activity of N-heterocyclic carbene (NHC) supported magnesium(II) and a zinc(II) amide complex towards the addition of N-H bond of amine to carbodiimide was studied. Treatment of a free carbene i.e., 1,3-di-tert-butylimidazol-2-ylidene (ItBu) with magnesium and zinc bis(amide) i.e., M[N(SiMe3)2]2, M = Mg or Zn in toluene led to the formation of ItBu:M[N(SiMe3) 2]2, M = Mg(1) and Zn(2) compounds, respectively. Both 1 and 2 were characterized by multinuclear (1H, 13C and 29Si) NMR spectroscopy and single X-ray crystal structure analysis. Solid state structures revealed that both complexes are monomeric in nature and their magnesium and zinc atoms are three coordinated and distorted trigonal planar in geometries. Furthermore, compounds 1 and 2 were tested as catalysts for the guanylation reaction of addition of amine to carbodiimide and turned to be excellent catalysts.
Catalytic guanylation of aliphatic, aromatic, heterocyclic primary and secondary amines using nanocrystalline zinc(II) oxide
Kantam, M. Lakshmi,Priyadarshini,Amal Joseph,Srinivas,Vinu,Klabunde,Nishina, Yuta
experimental part, p. 5730 - 5737 (2012/09/08)
Nanocrystalline ZnO was found to be a highly efficient heterogeneous catalyst for the guanylation of amines with various carbodiimides to afford N,N′,N″-trisubstituted guanidines in excellent yields. Structurally divergent aliphatic, aromatic, heterocyclic primary and secondary amines were converted to the corresponding N,N′,N″-trisubstituted guanidines using optimal conditions. The catalyst was easy to handle even under atmospheric conditions and can be easily recovered by centrifugation and reused for five cycles with consistent activity.
First iron-catalyzed guanylation of amines: A simple and highly efficient protocol to guanidines
Pottabathula, Srinivas,Royo, Beatriz
supporting information; experimental part, p. 5156 - 5158 (2012/09/22)
The first iron-catalyzed guanylation of amines is reported. Commercially available Fe(OAc)2 acts as an excellent catalyst for the addition of amines to carbodiimides. The reaction is broadly applicable to a variety of primary, secondary, and heterocyclic amines, and tolerates a wide range of functionalities allowing the easy preparation of a large family of guanidines. The low price and low toxicity of the commercially available iron catalyst make this methodology highly attractive.
Enol-functionalized N-heterocyclic carbene lanthanide amide complexes: Synthesis, molecular structures and catalytic activity for addition of amines to carbodiimides
Li, Zhi,Xue, Mingqiang,Yao, Haisheng,Sun, Hongmei,Zhang, Yong,Shen, Qi
experimental part, p. 27 - 34 (2012/08/07)
Reaction of LnCl3 (Ln = Y, Nd, Sm and Yb) with enol-functionalized imidazolium salt H2LBr (L = 4-OMe-C 6H4COCH{C(NCHCHNiPr)}) and NaN(TMS)2 at a molar ratio of 1:4:1 in THF at room temperature afforded the corresponding novel enol-functionalized N-heterocyclic carbene (NHC) lanthanide amides L 2LnN(TMS)2 (Ln = Y (1), Nd (2), Sm (3), Yb (4)) in 37-40% yields. Molecular structures of 1-4 were determined by X-ray structure analyses. All complexes adopt monomeric structures where each 5-coordinated metal is coordinated by two NHC ligands and one amido group.in distorted trigonal bipyramid geometry. All complexes, especially Yb complex (4), were found to be highly active precatalysts for the catalytic addition of amines to carbodiimides giving guanidines. The system with 4 shows good functional group tolerance and a wide scope of amines including primary and secondary cyclic amines.
Heterobimetallic dianionic guanidinate complexes of lanthanide and lithium: Highly efficient precatalysts for catalytic addition of amines to carbodiimides to synthesize guanidines
Zhang, Xingmin,Wang, Chuanyong,Qian, Cunwei,Han, Fubin,Xu, Fan,Shen, Qi
experimental part, p. 8790 - 8799 (2011/12/02)
A series of heterobimetallic dianionic guanidinate complexes of lanthanide and lithium, [Li(THF)(DME)]3Ln[μ- η2η1(iPrN)2C(NC 6H4p-R)]3 [R=Cl, Ln=Nd (I), Y (II), La (III); R=H, Ln=Nd (IV)] were synthesized and fully characterized. These complexes were found to be highly efficient precatalysts for the addition of various primary and secondary amines, and aromatic and aliphatic diamines to carbodiimides to give the corresponding monoguanidine and biguanidine derivatives under mild condition (at 25-60 °C), which provides an efficient way for the synthesis of biguanidines compounds. The activity depends on the central metals and ligands: La>Nd>Y for the metals and [(iPrN) 2C(NC6H4p-Cl)]2->[( iPrN)2C(NC6H5)]2- for the ligands were observed.
Ytterbium triflate: A highly active catalyst for addition of amines to carbodiimides to N,N′,N″-trisubstituted guanidines
Zhu, Xuehua,Du, Zhu,Xu, Fan,Shen, Qi
supporting information; experimental part, p. 6347 - 6349 (2009/12/08)
(Chemical Equation Presented) Ytterbium triflate was found to be efficient catalyst for addition of amines to carbodiimides to N,N′,N″- trisubstituted guanidines with a wide scope of amines under solvent-free condition.
Divalent lanthanide complexes: Highly active precatalysts for the addition of N-H and C-H bonds to carbodiimides
Du, Zhu,Li, Wenbo,Zhu, Xuehua,Xu, Fan,Shen, Qi
supporting information; experimental part, p. 8966 - 8972 (2009/04/06)
(Chemical Equation Presented) Various divalent lanthanide complexes with the formula LnL2(sol)x (L = N(TMS)2, sol = THF, x = 3, Ln = Sm (I), Eu (II), Yb (III); L = MeC5H4, sol = THF, x = 2, Ln = Sm (IV); L = ArO(Ar = [2,6-(tBu)2-4- MeC6H2]), sol = THF, x = 2, Ln = Sm (V)), especially complexes I-III, serve as excellent catalyst precursors for catalytic addition of various primary and secondary amines to carbodiimides, efficiently providing the corresponding guanidine derivatives with a wide range of substrates under solvent-free condition. The reaction shows good functional groups tolerence. Complexes I-III are also excellent precatalysts for addition of terminal alkynes to carbodiimides yielding a series of propiolamidines. The active sequence of Yb 5H4 2 for ligand around the metal was observed for both reactions. The first step in both reactions was supposed to include the formation of a bimetallic bisamidinate samarium species originating from the reduction-coupling reaction of carbodiimide promoted by lanthanide(II) complex. The active species is proposed to be a lanthanide guanidinate and a lanthanide amidinate.
Synthesis and diuretic activity of alkyl- and arylguanidine analogs of N,N'-dicyclohexyl-4-morpholinecarboxamidine in rats and dogs
Perricone,Humphrey,Skaletzky,Graham,Zandt,Zins
, p. 3693 - 3700 (2007/10/02)
Random screening identified N,N'-dicyclohexyl-4-morpholinecarboxamidine (U-18177, 1) as an orally effective nonkaliuretic diuretic in rats. The diuretic profile of 1 and its 1-adamantyl analog (U-37883A, 4) was confirmed orally in dogs, where they were less potent than standard diuretics but showed furosemide-like natriuresis at ≥100 μmol/kg. However, acute 1 at 61 and 90 μmol/kg iv resulted in lethal cardiac toxicity in dogs. Many analogs of 1 exhibited qualitatively similar diuretic profiles, but none was sufficiently safe to warrant development. Compound 1 also reversed minoxidil's vasodilation in dogs, which led to vascular interaction studies suggesting that analog 4 may block ATP-sensitive K channels. This K channel- blocking mechanism may contribute to the diuretic activity of the series. This is the first report broadly characterizing the diuretic activity of 1 and representative guanidine analogs in rats and dogs and its toxicity and minoxidil-blocking effects in dogs.
